• CELLMED
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• v.3 no.2
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• pp.18.1-18.7
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• 2013

Inflammation in rheumatoid arthritis is characterized by immune cell infiltration and cytokine secretion. In particular, mast cells and their cytokines play an important role in the pathogenesis of rheumatoid arthritis. Korean medicine, BaekJeol-Tang (BT) was designed by traditional Korean medicine theory. We already reported therapeutic effect of BT in rheumatoid arthritis. Here, we report the specific underlying mechanism of BT in activated human mast cells, HMC-1 cells. In addition, we report for the first time that BT significantly inhibited the production and mRNA expression of proinflammatory cytokines including thymic stromal lymphopoietin, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and tumor necrosis factor-${\alpha}$ in activated HMC-1 cells. BT also decreased the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and caspapase-1. Taken together, these results indicate that BT has potential as a regulator of inflammatory reactions for the treatment of arthritis such as osteoarthritis and rheumatoid arthritis.

• Journal of Applied Biological Chemistry
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• v.57 no.1
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• pp.1-5
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• 2014

The roots of Opuntia humifusa (OHR) were extracted with 80% aqueous MeOH and the concentrated extract was partitioned with EtOAc, n-butanol and $H_2O$, successively. The fractions were tested using DPPH and ABST radical scavenging method. The all fractions showed potent scavenging effects. The scavenging effect of the EtOAc fraction was higher than the other fractions, with $IC_{50}$ values as DPPH; $77.0{\pm}1.38{\mu}g/mL$, ABTS: $26.3{\pm}2.02{\mu}g/mL$. And, we investigated anti-inflammatory activities by examining the effects of the OHR fractions on pro-inflammatory cytokine release in the human mast cells (HMC-1). Treatment with OHR fractions clearly reduced the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, interleukin (IL)-6 and interleukin (IL)-8) in PMACI-stimulated HMC-1 cells. The results showed the potential of OHR as an excellent antioxidant substance and inhibiting inflammatory mediators. Therefore, OHR may be used as a therapeutic approach to various inflammatory diseases.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.1
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• pp.45-54
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• 2014

Lipopolysaccharide (LPS)-induced inflammatory responses in the HaCaT keratinocyte cell line produce proinflammatory cytokines, such as interleukin-1${\alpha}$(IL-1${\alpha}$), tumor neurosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and interleukin- 8 (IL-8) and also increase the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandins E2 (PGE2). In this study, we developed new natural ingredients for cosmetics that inhibit the pro-inflammatory responses induced by LPS in HaCaT cells. The mixture of Sorbus commixta (SC), Urtica dioica (UD), Phyllostachys nigra (PN), and Rhus semialata gall (RS) extracts blocked the increase of TNF-${\alpha}$ IL-1${\alpha}$ IL-6, and IL-8. The increase of COX-2, iNOS, and PGE2 were also blocked by it. Finally, the mixture inhibited skin irritation induced by sodium lauryl sulfate (SLS), when applied on skin through IQ chamber$^{(R)}$. In conclusion, these results show that the mixture of SC, UD, PN, and RS can be used as a primary ingredient to alleviate skin irritation when cosmeceutical products are developed for sensitive skin.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.168-174
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• 2010

Background: Sepsis still has a high mortality rate despite adequate supportive care. Newer therapeutic modalities have been developed but they have generally ended in failure. Recently, insulin was reported to have an anti-inflammatory effect by inhibiting the $I{\kappa}B/NF-{\kappa}B$ pathway, and may have therapeutic potential in sepsis. However, the precise mechanism of the anti-inflammatory effect of insulin is unclear. This study examined the role of insulin in activating $I{\kappa}B/NF-{\kappa}B$ in macrophage. Methods: Raw 264.7 cells, a murine macrophage cell line, were used in this experiment. Western blotting using $I{\kappa}B$ Ab and phosphor-specific $I{\kappa}B$ Ab was performed to evaluate the degradation and phosphorylation of $I{\kappa}B$ cells. For the $I{\kappa}B$ Kinase (IKK) activity, an immune complex kinase assay was performed. The level of interleukin-6 (IL-6) was measured by ELISA to determine the level of proinflammatory cytokine. Results: $I{\kappa}B{\alpha}$ degradation began 30 min after lipopolysaccharide (LPS) treatment. However, an insulin pretreatment suppressed the $I{\kappa}B{\alpha}$ degradation caused by the LPS treatment. The phosphorylation of $I{\kappa}B{\alpha}$ and IKK activity was also inhibited by the insulin pretreatment. Finally, the insulin pretreatment showed a tendency to suppress the induction of IL-6 by LPS. Conclusion: Insulin might have an anti-inflammatory effect though partial inhibition of the $I{\kappa}B/NF{\kappa}B$ pathway in macrophage cell lines.

• Journal of Periodontal and Implant Science
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• v.27 no.2
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• pp.425-441
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• 1997

The neuropeptide substance P(SP) has been implicated in the mediation of inflammation and immune-mediated disease such as arthritis. Recently, it was reported that SP was markedly increased around the blood vessels in inflamed gingiva as well as in close association with the inflammatory cell infiltrate. These results support that SP may contribute to the pathophysiology of neuronal inflammation in human periodontal tissues. SP may regulate inflammatory/immune responses by stimulating the proliferation of human T cells, differentiation and antibody-secreting potential of B cells, macrophage respiratory burst, connective tissue proliferation, and the secretion of cytokines from monocytes and T cells. Here, I studied potential role of SP as a costimulatory chemical signal in inflammatory/immune responses, by determining the released proinflammatory cytokines such as $MIP-1{\alpha}$, $IL-1{\beta}$, and IL-6 from culture supernatants of homogeneous immune cell lines. Serum free cell supernatants were concentrated with TCA precipitation, fractionated with SDS-PAGE, and subjected into western blot analysis. Among 15 cell lines tested, macrophage/monocyte cell line RAW264.7 and WRl9m.1 showed the highest level of induction of $MIP-1{\alpha}$ when stimulated with LPS. Discrete IL-6 bands with multiple forms of molecular mass were detected from supernatants of B cell lines A20(32kDa), Daudi(32, 35kDa), and SKW6.4(29kDa), which were expressed constitutively. $IL-1{\beta}$ could not be detected by the method of western blot analysis from supernatants of all cell lines tested except RAW264.7, WRl9m.1, and erythroid cell line K562 which showed the least amount of $IL-{\beta}$ secretion. SP $10^{-9}M$ with suboptimal dose of LPS treatment showed synergistic induction of $MIP-1{\alpha}$ release from RAW264.7 or WR19m.1, and also IL-6 release from A20, but this synergism is not the case in costimulation of RAW264.7 or WRl9m.1 with SP $10^{-9}M$ and TPA. Although treatment of T cell line CTLL-R8 with SP $10^{-7}M$ or PHA+TPA induced modest level of $MIP-1{\alpha}$ secretion, synergism was not observed when they are applied together. These findings all together suggest the possibility of a regulatory role of SP in inflammatory/immune reaction through differential modulation of bioactivities of other chemical cosignals.

• The Journal of Advanced Prosthodontics
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• v.3 no.3
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• pp.152-160
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• 2011

PURPOSE. This study was to investigate the effects of recombinant human platelet-derived growth factor (rhPDGF-BB) and heparin to titanium surfaces for enhancement of osteoblastic functions and inhibition of inflammation activity. MATERIALS AND METHODS. The anodized titanium discs, not coated with any material, were used as a control group. In heparinized-Ti group, dopamine was anchored to the surface of Ti substrates, and coated with heparin. In PDGF-Ti group, rhPDGF-BB was immobilized onto heparinized Ti surface. The surface morphologies were investigated by the scanning electron microscope in each group. The release kinetics of rhPDGF-BB were analyzed, and cytotoxicity tests for each group were conducted. The biocompatibilities were characterized by measuring cell proliferation, alkaline phosphatase activity, and calcium deposition using MG-63 cells. Statistical comparisons were carried out by one-way ANOVA tests. Differences were considered statistically significant at $^*$P<.05 and $^{**}$P<.001. RESULTS. The combination of rhPDGF-BB and heparin stimulated alkaline phosphatase activity and OCN mRNA expression in osteoblastic cells ($^*$P<.05 and $^{**}$P<.001). MG-63 cells grown on PDGF-Ti had significantly higher amounts of calcium deposition than those grown on anodized Ti ($^{**}$ P<.001). Heparinized Ti was more anti-inflammatory compared to anodized Ti, when exposed to lipopolysaccharide using the transcript levels of TNF-${\alpha}$ and IL-6 of proinflammatory cytokine ($^*$P<.05 and $^{**}$P<.001). CONCLUSION. The result of this study demonstrated that the incorporation of rhPDGF-BB and heparin onto Ti surface enhanced osteoblastic functions and inhibited inflammation.

• Clinical and Experimental Pediatrics
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• v.56 no.11
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• pp.482-489
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• 2013

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1379-1387
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• 2013

In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha ($TNF{\alpha}$) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of $TNF{\alpha}$ gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03). The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the $TNF{\alpha}$-824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after birth of a heifer calf increases the probability of culling for the cows with the G/G genotype in animal husbandry.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.191-198
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• 2017

Hyaluronidase inhibitory activity as inflammatory factor of Koreinsis chinensis leaf ethanol extract was showed higher inhibitory activity than water extract. 29.5% inhibitory activity was shown at concentration of $200{\mu}g/mL$ phenolics. Lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were treated with different concentrations ($5-25{\mu}g/mL$) of Koreinsis chinensis leaf extract and the amount of nitric oxide (NO) was determined; LPS-treated cells produced 3 times more NO than non-LPS treated cells. Moreover, the NO production in cells treated with Koreinsis chinensis leaf extract showed inhibitory effect in a concentration-dependent manner. Due to the stimulant-induced NO production is regulated by the inducible nitric oxide synthase (iNOS), we determined the iNOS protein level to elucidate the mechanism by which the NO production was inhibited. It was reduced by 40% with a Koreinsis chinensis leaf extract concentration of $25{\mu}g/mL$ and identified iNOS inhibition in dose-dependent manner. The prostaglandin $E_2$ production in cells treated with Koreinsis chinensis leaf extract was reduced by 26.2% at concentration of $25{\mu}g/mL$. The protein expression of cyclooxygenase-2 in LPS-treated Raw 264.7 cells was inhibited by 64% at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Koreinsis chinensis leaf extract had a concentration-dependent inhibitory effect on the production of tumor necrosis factor-${\alpha}$ and interleukin-6 as pro-inflammatory cytokine in LPS-treated Raw 264.7 cells at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Their levels were decreased by 61.7 and 62% respectively.

• Korean Journal of Food Science and Technology
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• v.46 no.6
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• pp.773-777
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• 2014

The anti-inflammatory activity of onion juices prepared from sulfur-fertilized onions was investigated by measuring the secretion of proinflammatory cytokines from human monocytes cultured under hyperglycemic condition. Human monocytic (THP-1) cells were cultured under normoglycemic (NG, 5.5 mM glucose) or hyperglycemic (HG, 25 mM glucose) conditions, with or without onion juice. Without onion juice, cell viability decreased significantly in the HG state for 48 h, compared to that in the NG state. With onion juice ($50-150{\mu}L$) treatment, the cell viability was not different from that under the NG condition, suggesting that onion juice prevented HG-induced monocytes cytotoxicity. While the HG condition in vitro significantly induced TNF-${\alpha}$ release from THP-1 cells and its gene expression, onion juice ($50{\mu}L$) significantly suppressed them. This indicates that onion juice inhibited HG-induced cytokine production in monocytes. These results suggest that onion juice from sulfur-fertilized onions can be used for the prevention of diabetes and related diseases.